George Hogarth
Introduction
Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a generally asymptomatic and benign congenital hamartoma of the retina. It presents as 3 variants: solitary (unifocal), grouped and atypical (1).
The variant of CHRPE which is related to Familial Adenomatous Polyposis (FAP) is the atypical type. FAP consists of numerous adenomatous polyps of the colon and rectum. Untreated individuals with FAP almost always develop colorectal cancer by middle age. Atypical CHRPE is also associated with Gardner syndrome, a variant of FAP characterised by a constellation of colonic polyps, osteomas, soft tissue tumours and dental abnormalities.
It is not uncommon for the other types to be misdiagnosed as being related to FAP. Because CHRPEs are reasonably common when viewing the fundus it is beneficial to be able to recognise the features of atypical CHRPEs to reduce the chance of misdiagnosis and overtreatment.
Epidemiology
The prevalence of CHRPE has been estimated to be between 1-4%.
Histopathology
Most solitary and grouped CHRPEs are a monocellular layer of hypertrophied RPE cells packed densely with large macromelanosomes. Over time, it is not uncommon for CHRPEs to depigment. When this happens, RPE cells are replaced by glial cells. This can sometimes lead to a thickening in Bruch’s membrane.
Atypical CHRPE lesions demonstrate RPE hypertrophy and hyperplasia, retinal invasion, and retinal vascular changes (1).
Diagnosis
The diagnosis can normally be made clinically using fundoscopy. Wide field fundus photography can be useful for documentation.
Ancillary testing can be beneficial when uncertainty exists.
The following diagnostic findings are typical in CHRPEs:
- Fundus autofluorescence: hypoautofluorescence as a result of high melanin content.
- Fluorescein angiography (FA) or indocyanine green angiography (ICGA): No leakage. The lesions normally block underlying choroidal fluorescence.
- Optical coherence tomography: Loss of RPE, retinal thinning and increased transmission in areas of lacunae. Hypertrophic areas of the lesion have thickened hyperreflective RPE with overlying photoreceptor loss.
The three types
Solitary
Classic CHRPE is unifocal and usually located in the mid-periphery of the fundus. The colour can vary from light grey to black with there being distinct edges between the CHRPE and bordering RPE. They are normally flat and round in shape. It is possible for retinal thinning to occur. Vision loss can also occur if the lesion is at the macula. It is normal for lesions to grow in size over time. Malignant transformation is rare and no reports of metastasis exist (2).
Grouped (Multifocal)
Grouped lesions may contain up to 30 lesions which can range in size from 100–300 μm. The lesions are normally localised to one quadrant of the retina. They have the appearance of animal tracks and are sometimes referred to as ‘bear tracks’. The size of the lesions normally increase towards the periphery. No halos are present. This subtype of CHRPE is usually confused with the atypical type.
Atypical
Atypical CHRPEs are generally smaller (50–100 μm) than single lesions. They possess an oval, spindle or pisiform shape and are spread randomly across the fundus. In approximately 80% of cases they are bilateral. Bigger lesions can be surrounded by depigmented haloes.
Management by Ophthalmologist
It is sensible to refer a patient for a gastrointestinal opinion if any of the following are present:
- Bilateralism
- Occurrence in multiple quadrants
- Irregular borders
- Pisiform shape
- A family history of FAP, colorectal polyps, or early colorectal cancer
Gastrointestinal investigations include colonoscopy (with biopsy) and genetic testing. Genetic screening is recommended when colonoscopy reveals greater than ten polyps. The tumour suppressor gene APC is responsible for FAP. The inheritance pattern is autosomal dominant.
Conclusion
Although atypical CHRPEs associated with FAP are very rare, it is important to be able to differentiate this type from the more common benign variant. Missed diagnoses can, unfortunately, have severe consequences. Identification of patients with FAP-associated CHRPE as a result of de novo APC mutations is particularly important, as there is a high chance of invasive adenocarcinoma at a young age. A multidisciplinary approach involving ophthalmologists, gastroenterologists, geneticists, and primary care physicians remains essential for the effective identification and management of individuals at risk.
References
- Congenital Hypertrophy of the Retinal Pigment Epithelium – EyeWiki [Internet]. eyewiki.org. Available from: https://eyewiki.org/Congenital_Hypertrophy_of_the_Retinal_Pigment_Epithelium
- Deibert B, Ferris L, Sanchez N, Weishaar P. The link between colon cancer and congenital hypertrophy of the retinal pigment epithelium (CHRPE). Am J Ophthalmol Case Rep. 2019 Jul 24;15:100524